PROJECT SUMMARY - CLINICAL CORE The prevalence of HAND in HIV+ individuals with advanced infection remains around 40-50%, and HAND may now be the most common form of young-age neurocognitive impairment globally. Currently there are no uniformly accepted clinical, neuroimaging, or laboratory outcome measures for clinical trials for the treatment of HAND. This Core provides the support necessary to evaluate new outcome measures of CNS function including both neurocognitive assessments (e.g., screening tests for HAND) and performance based functional assessments. In addition, the Core will provide well-characterized individuals for developmental projects such as novel neuroimaging outcomes which may be more sensitive to CNS dysfunction and response to treatment than neuropsychological test measures. The Clinical Core will also provide well-characterized individuals for evaluating novel laboratory markers identified in the Biomarker Core. Specifically, we will examine markers of cell stress, neuronal injury, and energy metabolism, which are also being used as platforms for therapeutic targets in our Therapeutic Core. The goals and objectives of this Core are as follows: 1) To maintain a clinical cohort of well-characterized HIV+ and demographically-matched HIV- individuals to improve the efficiency of accruing and conducting clinical trials, 2) To liaise with other NIMH Centers, other funded IPCPs, the AIDS Clinical Trials Group (ACTG), the Johns Hopkins University Center for AIDS Research (JHU CFAR), Institute for Clinical and Translational Research (ICTR), and the Johns Hopkins University (JHU) Drug Discovery unit to assist in the development of interventional therapeutics for HAND, 3) To provide the infrastructure and resources necessary to conduct small early phase studies to evaluate therapeutics for HAND including novel drugs, neuromodulation and behavioral strategies, 4) To maintain a data infrastructure to allow for efficient querying of clinical and laboratory data, 5) To provide statistical support for all studies involving the Center Grant resources.